Quantitative detection of target sequences (e.g., alleles, polymorphisms, etc.) in a nucleic acid sample is useful in a variety of contexts. For example, detection of rare target sequences can be useful for early, benign, or malignant tumor detection or monitoring; prenatal diagnostics, such as non-invasive fetal diagnostics; detection of viral or bacterial infection; environmental monitoring, and the like. In some cases, such detection requires a high level of sensitivity, accuracy, and precision in order to detect low abundance target sequences in a background of highly abundant non-target sequences.